Long-range goal: 1. To provide an understanding of fast local and lateral gain control mechanisms in the human retina. 2. To lay the foundation applications of a new and powerful functional imaging technique for the noninvasive detection of inner retinal dysfunction in early stages of glaucoma and in diabetes. Recent progress: During the previous project periods, the concept of functional imaging of the retina by means of a multifocal technique based on multi-input nonlinear systems analysis has been explored and the technique has been established as a valuable scientific and clinical too. Our studies were aimed at the detection and mapping of local retinal dysfunction, and the identification and characterization of sources of the electroretinogram and the VEP. Patient studies included glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, optic neuropathy as well as some infection diseases. The study of ERG components reflecting inner retinal function and the detection and mapping of changes in these components in glaucoma and diabetes has become a major focus of this project. Much progress has been made toward the extraction and mapping of signals from ganglion cells. A notable achievement was the development of methods for the enhancement and extraction of a component from ganglion cell axons nears the nerve head. VEP studies included isolation of M and P components in the cortical response and multifocal source localization (collaboration). Specific aims for the next project period: 1. To determine dynamics and lateral spread of nonlinear adaptive mechanisms in the human retina using new techniques developed during the last project period. 2. T detect and image the loss of ganglion cell responses in glaucoma using the multifocal ERG. Different modes of stimulation, signal derivation and analysis techniques will be compared using a small number of patients and normals. The best protocol will be evaluated on larger populations of patients and normals. 3. To test the hypothesis that the range and dynamics of the components investigated under 1. are sensitive indicators of retinal ischemia in diabetes. To develop a method to map functional changes in diabetes.